5673-40-5

Upstream product

• 127-27-5 pimaric acid 
• 917-64-6 methyl magnesium iodide 

Relevant academic research and scientific papers

Molecular basis of pimarane compounds as novel activators of large-conductance Ca2+-activated K+ channel α-subunit

Effects of pimaric acid (PiMA) and eight closely related compounds on large-conductance K+ (BK) channels were examined using human embryonic kidney (HEK) 293 cells, in which either the α subunit of BK channel (HEKBKα) or both α and β1 (HEKBKαβ1) subunits were heterologously expressed. Effects of these compounds (10 μM) on the membrane potential of HEKBKαβ1 were monitored by use of DiBAC4(3), a voltage-sensitive dye. PiMA, isopimaric acid, sandaracoisopimaric acid, dihydropimaric acid, dihydroisopimaric acid, and dihydroisopimarinol induced substantial membrane hyperpolarization. The direct measurement of BKαβ1 opening under whole-cell voltage clamp showed that these six compounds activated BKαβ1 in a very similar concentration range (1-10 μM); in contrast, abietic acid, sclareol, and methyl pimarate had no effect. PiMA did not affect the charybdotoxin-induced block of macroscopic BKαβ1 current. Single channel recordings of BKαβ1 in inside-out patches showed that 10 μM PiMA did not change channel conductance but significantly increased its open probability as a result of increase in sensitivity to Ca2+ and voltage. Because coexpression of the β1 subunit did not affect PiMA-induced potentiation, the site of action for PiMA is suggested to be BKα subunit. PiMA was selective to BK over cloned small and intermediate Ca2+ activated K+ channels. In conclusion, PiMA (gt;1 μM) increases Ca2+ and voltage-sensitivity of BKα when applied from either side of the cell membrane. The marked difference in potency as BK channel openers between PiMA and abietic acid, despite only very small differences in their chemical structures, may provide insight into the fundamental structure-activity relationship governing BKα activation.